Apparatus for outer wall focusing for high volume fraction particle microfiltration and method for manufacture thereof

Abstract

An apparatus for microfiltration and a scalable method for manufacture of an inertial microfluidic device for such microfiltration apparatus are provided. The apparatus for microfiltration includes one or more inertial microfluidic devices, each including a plurality of spirals of a microfluidic channel. At least one of the inertial microfluidic devices is configured to utilize outer wall focusing for high volume fraction microfiltration of particles. In an embodiment, multiple inertial microfluidic devices are connected in sequence for combined inner wall and outer wall focusing. The scalable method for manufacture of the inertial microfluidic device includes micromachining on a polycarbonate-based substrate a rectangular spiral microchannel having one or more input channels and a plurality of output channels configured to utilize high volume fraction outer wall focusing for microfiltration of particles.

What is claimed is: 
     
         1 . An apparatus for microfiltration comprising:
 one or more inertial microfluidic devices comprising a plurality of spirals of a microfluidic channel wherein at least a first one of the one or more inertial microfluidic devices is configured to utilize outer wall focusing for high volume fraction microfiltration of fluid having particles.   
     
     
         2 . The apparatus in accordance with  claim 1  wherein the fluid comprises a liquid or media. 
     
     
         3 . The apparatus in accordance with  claim 1  wherein the high volume fraction microfiltration of fluid comprises the high volume fraction microfiltration at a predetermined flow rate. 
     
     
         4 . The apparatus in accordance with  claim 3  wherein the predetermined flow rate is greater than one-quarter milliliter per minute. 
     
     
         5 . The apparatus in accordance with  claim 1  wherein the high volume fraction microfiltration of the media comprises high volume fraction microfiltration of the media at a volume fraction greater than one percent (1%). 
     
     
         6 . The apparatus in accordance with  claim 5  wherein the high volume fraction microfiltration of the media comprises high volume fraction microfiltration of the media at a volume fraction greater than 1.7%. 
     
     
         7 . The apparatus in accordance with  claim 6  wherein the high volume fraction microfiltration of the media comprises high volume fraction microfiltration of the media at a volume fraction greater than five percent (5%). 
     
     
         8 . The apparatus in accordance with  claim 1  wherein the at least a first one of the one or more inertial microfluidic devices comprises a first predetermined number of inlets coupled via the microfluidic channel to a second predetermined number of outlets, wherein at least one of the second predetermined number of outlets is configured to provide an output of an outer wall filtrated portion of the particles. 
     
     
         9 . The apparatus in accordance with  claim 8  wherein the at least one of the second predetermined number of outlets configured to provide the output of the outer wall filtrated portion of the particles has a width greater than other ones of the second predetermined number of outlets, and wherein widths of each of the second predetermined number of outlets is between one-tenth of a width of the microfluidic channel and one-half of the width of the microfluidic channel. 
     
     
         10 . The apparatus in accordance with  claim 9  wherein the second predetermined number of outlets comprises two outlets, and wherein a first outlet is an outer wall focused outlet configured to provide the output of the outer wall filtrated portion of the particles and a second outlet is an inner wall focused outlet. 
     
     
         11 . The apparatus in accordance with  claim 1  wherein at least a second one of the one or more inertial microfluidic devices is configured to utilize inner wall focusing for microfiltration of particles. 
     
     
         12 . The apparatus in accordance with  claim 11  wherein the at least a second one of the one or more inertial microfluidic devices comprises a first predetermined number of inlets coupled via the plurality of spirals of the microfluidic channel to a second predetermined number of outlets, wherein the second predetermined number is greater than the first predetermined number and at least one of the second predetermined number of outlets has a width greater than other ones of the second predetermined number of outlets to provide an output of an inner wall filtrated portion of the particles. 
     
     
         13 . The apparatus in accordance with  claim 12  wherein the second predetermined number of outlets comprises two outlets, and wherein a first outlet is an inner wall focused outlet and the second outlet is outer wall focused outlet, and wherein the inner wall focused outlet is the at least one of the second predetermined number of outlets which has a width greater than the outer wall focused outlet. 
     
     
         14 . The apparatus in accordance with  claim 13  where a width of the inner wall focused outlet is substantially two-thirds of the width of the microfluidic channel and a width of the outer wall focused outlet is substantially one-third of the width of the microfluidic channel. 
     
     
         15 . The apparatus in accordance with  claim 14  wherein the one or more inertial microfluidic devices comprise one or more groups of three inertial microfluidic devices and wherein a first one of each group of three inertial microfluidic devices comprises an inertial microfluidic device configured to utilize outer wall focusing for microfiltration of particles by having a first predetermined number of spirals of a microfluidic channel connecting one inlet to two outlets, a first outlet being an outer wall focused outlet having a width substantially two-thirds of the width of the microfluidic channel and a second outlet being an inner wall focused outlet having a width substantially one-third of the width of the microfluidic channel, and
 wherein a second one and a third one of each group of three inertial microfluidic devices each comprise an inertial microfluidic device configured to utilize inner wall focusing for microfiltration of particles by having a respective second and third predetermined number of spirals of a microfluidic channel connecting one inlet to two outlets, wherein the two outlets comprise an inner wall focused outlet and an outer wall focused outlet and wherein the inner wall focused outlet has a width substantially two-thirds of the width of the rectangular microfluidic channel and the outer wall focused outlet has a width substantially one-third of the width of the microfluidic channel, and 
 wherein the inlet of the first one of each group of three inertial microfluidic devices is configured to receive an input of unfiltered media having particles, and 
 wherein the inlet of the second one of each group of three inertial microfluidic devices is configured to receive an input of filtered media from the inner wall focused outlet of the first one of each group of three inertial microfluidic devices, and 
 wherein the inlet of the third one of each group of three inertial microfluidic devices is configured to receive an input of filtered media from the inner wall focused outlet of the second one of each group of three inertial microfluidic devices, and 
 wherein the filtered media output from the inner wall focused outlet of the third one of each group of three inertial microfluidic devices is provided as an output from the group of three inertial microfluidic devices. 
 
     
     
         16 . The apparatus in accordance with  claim 15  wherein each of the first predetermined number of spirals, the second predetermined number of spirals and the third predetermined number of spirals are selected from the group comprising five spirals, six spirals and seven spirals. 
     
     
         17 . The apparatus in accordance with any of the preceding claims wherein the apparatus for microfiltration comprises a continuous apheresis device using microfluidics for separating blood constituents at high hematocrit without pre-dilution. 
     
     
         18 . The apparatus in accordance with any of the preceding claims wherein the apparatus for microfiltration comprises a small volume blood centrifuge. 
     
     
         19 . The apparatus in accordance with any of the preceding claims wherein the apparatus for microfiltration comprises a perfusion microbioreactor for providing continuous perfusion filtration. 
     
     
         20 . The apparatus in accordance with any of the preceding claims wherein the apparatus for microfiltration comprises a small-scale perfusion filter, the perfusion filter further comprising:
 a bioreactor configured to receive an input of media comprising particles for perfusion and coupled to the one or more inertial microfluidic devices for providing a perfused output thereto, and   
       wherein the one or more inertial microfluidic devices filter the perfused output of the bioreactor to provide a harvested output of the media. 
     
     
         21 . The apparatus in accordance with  claim 20  wherein the one or more inertial microfluidic devices are further coupled to the bioreactor to feed back a cell concentrate to the bioreactor. 
     
     
         22 . The apparatus in accordance with any of the preceding claims wherein the microfluidic channel of each of the one or more inertial microfluidic devices comprises a rectangular spiral microchannel having one or more input channels and a plurality of output channels micromachined on a rigid material. 
     
     
         23 . The apparatus in accordance with  claim 22  wherein the rigid material comprises a material selected from a polycarbonate-based substrate, a material comprising polycarbonate, or a thermoplastic material. 
     
     
         24 . A method for manufacture of an inertial microfluidic device comprising micromachining on a rigid substrate a rectangular spiral microchannel having one or more input channels and a plurality of output channels configured to utilize outer wall focusing for high volume fraction microfiltration of particles. 
     
     
         25 . The method in accordance with  claim 24  wherein the plurality of output channels include at least an outer wall focused output channel, and wherein the inertial microfluidic device is configured to utilize outer wall focusing for high volume fraction microfiltration of particles by micromachining the outer wall focused output channel to have a width greater than widths of all other ones of the plurality of output channels.